Please use this identifier to cite or link to this item: http://hdl.handle.net/1783.1/3222

JAK1-STAT1-STAT3, a key pathway promoting proliferation and preventing premature differentiation of myoblasts

Authors Sun, Luguo
Ma, Kewei
Wang, Haixia
Xiao, Fang
Gao, Yan
Zhang, Wei
Wang, Kepeng
Gao, Xiang
Ip, Nancy
Wu, Zhenguo
Issue Date 2007
Source JOURNAL OF CELL BIOLOGY , v. 179, (1), 2007, OCT 8, p. 129-138
Summary Skeletal muscle stem cell-derived myoblasts are mainly responsible for postnatal muscle growth and injury-induced muscle regeneration. However, the cellular signaling pathways controlling the proliferation and differentiation of myoblasts are not fully understood. We demonstrate that Janus kinase 1 (JAK1) is required for myoblast proliferation and that it also functions as a checkpoint to prevent myoblasts from premature differentiation. Deliberate knockdown of JAK1 in both primary and immortalized myoblasts induces precocious myogenic differentiation with a concomitant reduction in cell proliferation. This is caused, in part, by an accelerated induction of MyoD, myocyte enhancer-binding factor 2 (MEF2), p21Cip1, and p27Kip1, a faster down-regulation of Id1, and an increase in MEF2-dependent gene transcription. Downstream of JAK1, of all the signal transducer and activator of transcriptions (STATs) present in myoblasts, we find that only STAT1 knockdown promotes myogenic differentiation in both primary and immortalized myoblasts. Leukemia inhibitory factor stimulates myoblast proliferation and represses differentiation via JAK1-STAT1-STAT3. Thus, JAK1-STAT1-STAT3 constitutes a signaling pathway that promotes myoblast proliferation and prevents premature myoblast differentiation.
Subjects
ISSN 0021-9525
Rights Journal of cell biology © copyright 2007 Rockefeller University Press. The journal's Web site is located at http://intl.jcb.org/
Language English
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